Are we standing on the shifting sands of post-transplant metabolic-associated steatotic liver disease?

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the predominant global cause of chronic liver disease and represents a major indication for liver transplantation. Post-transplant MASLD manifests as recurrent disease in nearly all recipients by five years post-transplantation, while de novo MASLD shows variable incidence (18%-78%). Although histologically similar, recurrent MASLD follows a more aggressive trajectory, with accelerated fibrosis and cirrhosis. Metabolic disturbances, immunosuppression regimens, donor-related factors, and chronic inflammation synergistically contribute to disease pathogenesis. The disorder not only compromises graft function but is also associated with elevated cardiovascular and overall morbidity, and malignancy risk. Despite advancements in noninvasive diagnostics, histopathology remains essential for definitive diagnosis and prognostic stratification. Management should prioritize metabolic optimization, lifestyle intervention, and tailored immunosuppressive regimens. Glucagon-like peptide-1 receptor agonists represent a promising therapeutic avenue. However, the absence of standardized, transplant-specific guidelines is a significant limitation. Further research is necessary to define diagnostic criteria, risk stratification, and targeted therapy to improve graft survival and patient outcomes.

Keywords: Metabolic syndrome; Steatotic liver disease; Metabolic dysfunction-associated steatotic liver disease; Liver transplantation; Recurrence; Outcomes

Core Tip: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the fastest-growing indication for liver transplantation (LTx) in Western countries, and the recurrence rate approaches 100% at 5 years. Recurrent disease progresses faster than native liver MASLD and is driven by immunosuppression-mediated metabolic dysregulation. Immunosuppressive regimens may have limitations, and even though there is need for tailored strategies, evidence is lacking for their application in post-LTx MASLD. Histological assessment remains essential for risk stratification despite advances in noninvasive diagnostics. Optimized immunosuppression, metabolic control, and emerging therapies are key research priorities to improve outcomes. Standardized guidelines for post-LTx MASLD management are urgently needed.